Influence of the Estrous Cycle on c-fos and CRH Gene Transcription in the Brain of Endotoxin-Challenged Female Rats
Bibliographic record
Abstract
The purpose of this study was to investigate whether the ovulatory cycle interferes with the effect of the acute-phase response of a systemic immune activation on the transcription of the immediate early gene c-fos and the stress-related neuropeptide corticotropin-releasing hormone (CRH) in the brains of female rats. Throughout the day of proestrus and diestrus-2 (09.00, 12.00, 15.00 h), adult rats received either a single intraperitoneal injection of the endotoxin lipopolysaccharide (LPS, 200 micrograms/100 g body weight) or the vehicle solution and were killed 3 h later (12.00, 15.00, 18.00 h). Frozen brains were mounted on a microtome, cut in 30-micron slices and then processed for the detection of c-fos mRNA and CRH primary transcript (heteronuclear [hnRNA]) by means of in situ hybridization histochemistry using 35S-labeled exonic and intronic probes, respectively. LPS injection induced a profound expression of c-fos mRNA in the several nuclei and areas of the brain, such as the organum vasculosum of the lamina terminalis/medial preoptic area, supraoptic nucleus, parvo- and magnocellular divisions of the hypothalamic paraventricular nucleus (PVN), arcuate nucleus/median eminence, central nucleus of the amygdala, locus coeruleus, nucleus of the solitary tract, area postrema and ventrolateral medulla. Interestingly, the intensity of expression of c-fos mRNA depended on the phase of the estrous cycle and/or the time of the day. Indeed, in several of the structures described above, LPS induced a more pronounced c-fos signal in the morning of proestrus than the afternoon and diestrus-2. CRH primary transcript was significantly increased by LPS treatment selectively in the parvocellular division of the PVN and the highest hybridization signal was observed in the morning of proestrus, a period where a large number of c-fos-positive cells were colocalized in CRH-immunoreactive neurons. A significant increase in the levels of AVP hnRNA was also observed in the parvocellular PVN of animals sacrificed at noon and early afternoon of both pro- and diestrus days. These results provide evidence that the neuroendocrine events regulating the reproductive cyclicity influence the endotoxin-induced activation of the early gene c-fos in selective structures of the brain and the stimulation of neurons directly involved in the regulation of the HPA axis. It is possible that the gonadal status of female mammals plays a crucial role in the integration of the organism in the presence of foreign material in preventing an exaggerated immune response during particular phases of the ovulatory cycle. The capacity of female animals to modulate the intensity through which the neuronal circuitry activated during immunogenic processes is likely to be an elegant sexual dimorphism participating in the adjustment of the responses in line with the physiological demand.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".